Liver dysfunction as a respiratory prognostic factor in covid-19 patients.

Respiratory dysfunction is a main clinical symptom of COVID-19. Liver dysfunction is also frequently reported in patients with COVID-19 and considered to be related to a poor prognosis. However, the precise mechanisms behind these findings remain unclear. We investigated the clinical features and prognostic factors related to liver dysfunction in 26 COVID-19 pa-tients. The patients with liver dysfunction had markedly higher WBC, neutrophils, CRP, and frequency of oxygen administration and markedly lower PaO2/FIO2 ratios. The patients with liver dysfunction had longer mean hospital stays. In conclusion, liver dysfunction at hospital admission may be an important prognostic factor for respiratory failure in patients with COVID-19. We must administer intensive care to these patients earlier to inhibit severe disease progression.Copyright ©2021 The Japan Society of Hepatology.

Dendritic Cell Subsets in Melanoma: Pathophysiology, Clinical Prognosis and Therapeutic Exploitation.

Evasion from immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells shaping anti-tumor immune responses, but tumor cells exploit DC versatility to subvert their functions. Unveiling the puzzling role of DCs in the control of tumor development and mechanisms of tumor-induced DC hijacking is critical to optimize current therapies and to design future efficient immunotherapies for melanoma. Dendritic cells, crucially positioned at the center of anti-tumor immunity, represent attractive targets to develop new therapeutic approaches. Harnessing the potencies of each DC subset to trigger appropriate immune responses while avoiding their subversion is a challenging yet promising step to achieve tumor immune control. This review focuses on advances regarding the diversity of DC subsets, their pathophysiology and impact on clinical outcome in melanoma patients. We provide insights into the regulation mechanisms of DCs by the tumor, and overview DC-based therapeutic developments for melanoma. Further insights into DCs' diversity, features, networking, regulation and shaping by the tumor microenvironment will allow designing novel effective cancer therapies. The DCs deserve to be positioned in the current melanoma immunotherapeutic landscape. Recent discoveries strongly motivate exploitation of the exceptional potential of DCs to drive robust anti-tumor immunity, offering promising tracks for clinical successes.

The relationship between mortality and inflammatory markers and the systemic immune inflammatory index in patients in the intensive care unit with a pneumothorax as a complication of COVID-19 disease.

BACKGROUND: A pneumothorax is common in patients admitted to the intensive care unit (ICU) with coronavirus disease (COVID-19) when non-invasive or invasive mechanical ventilation is performed to maintain adequate oxygenation. The aim of the present study was to investigate the effects of elevated inflammatory markers and an elevated systemic immune inflammatory index (SII) on mortality in this patient population. MATERIALS AND METHODS: Between March 2020 and May 2021, 124 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reacion positviity who were admitted to the ICU in our hospital and diagnosed with and treated for a pneumothorax were evaluated retrospectively. Interleukin-6 (IL-6), C-reactive protein, neutrophil, lymphocyte, platelet and white blood cell levels were measured. These parameters were used to calculate the neutrophil-lymphocyte ratio (NLR) and SII, and the association of these parameters with pneumothorax-related mortality was examined. RESULTS: This study included 39 female (31.5%) and 85 male (68.5%) patients. The mean age was 65.3 ± 12.6 years. Non-invasive mechanical ventilation was performed in 13 (10.5%) patients, and 111 (89.5%) patients received invasive mechanical ventilation. Tube thoracostomy was performed in 113 patients (91.1%), and 11 patients (8.9%) were treated with oxygen therapy. The factors affecting mortality in the pneumothorax patients were the Charlson Comorbidity Index (four or higher), IL-6 level and NLR. The IL-6 level was 53.4 in those who died versus 24.6 in those who survived (p = 0.017). The NLR in the patients who died was 16.9 as compared to 12.5 in those who survived (p = 0.011). CONCLUSION: Elevated markers of infection were associated with an increased risk of mortality in pneumothorax patients with COVID-19 who received invasive or non-invasive mechanical ventilation in the ICU. In this patient population, high levels of positive end-expiratory pressure should be avoided, and inflammatory marker levels and the SII should be closely monitored.

Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019.

OBJECTIVES: Many biomarkers have been studied to assist in the risk stratification and prognostication of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Procalcitonin (PCT), a circulating precursor of the hormone calcitonin, has been studied with mixed results as a predictor of severe coronavirus disease 2019 (COVID-19) in the general population; however, to date, no studies have focused on the utility of PCT in predicting disease severity and death from COVID-19 in the cancer population. METHODS: We conducted a retrospective study of cancer patients hospitalized with COVID-19 at a comprehensive cancer center over a 10-month period who had PCT recorded on admission. We assessed associations between variables of clinical interest and the primary outcomes of progression of COVID-19 and death during or within 30 days of hospitalization using univariable and multivariable logistic regression. RESULTS: The study included 209 unique patients. In the univariate analysis, elevated PCT on admission was associated with higher odds of progression of COVID-19 or death (Odds ratio [OR] 1.40, 95% CI 1.08-1.93) and mortality alone (OR 1.53, 95% CI 1.17-2.11). In multivariate regression, PCT remained significantly associated with progression or death after holding chronic kidney disease (CKD) status constant (OR 1.40, 95% CI: 1.08, 1.93, p=0.003). Similarly, the association of PCT and death remained significant after adjusting for age (OR 1.54, 95% CI: 1.17-2.15). CONCLUSIONS: In hospitalized COVID-19 patients with underlying cancer, initial PCT levels on admission may be associated with prognosis, involving higher odds of progression of COVID-19 and/or mortality.

Clinical Characteristics and Risk Prediction Score in Patients With Mild-to-Moderate Coronavirus Disease 2019 in Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, causing widespread mortality. Many patients with COVID-19 have been treated in homes, hotels, and medium-sized hospitals where doctors were responsible for assessing the need for critical care hospitalization. This study aimed to establish a severity prediction score for critical care triage. METHOD: We analyzed the data of 368 patients with mild-to-moderate COVID-19 who had been admitted to Fussa Hospital, Japan, from April 2020 to February 2022. We defined a high-oxygen group as requiring ≥4 l/min of oxygen. Multivariable logistic regression was used to construct a risk prediction score, and the best model was selected using a stepwise selection method. RESULTS: Multivariable analysis showed that older age (≥70 years), elevated creatine kinase (≥127 U/L), C-reactive protein (≥2.19 mg/dL), and ferritin (≥632.7 ng/mL) levels were independent risk factors associated with the high-oxygen group. Each risk factor was assigned a score ranging from 0 to 4, and we referred to the final overall score as the Fussa score. Patients were classified into two groups, namely, high-risk (total risk factors, ≥2) and low-risk (total risk score, <2) groups. The high-risk group had a significantly worse prognosis (low-risk group, undefined vs. high-risk group, undefined; P< 0.0001). CONCLUSIONS: The Fussa score might help to identify patients with COVID-19 who require critical care hospitalization.

Impact of glycemia and insulin treatment in fatal outcome of severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. How the glucose level might affect the clinical outcome remains obscure. METHODS: A multicenter study was performed in 2 hospitals from 2011 to 2021. Patients with SFTS and acute hyperglycemia (admission fasting plasma glucose [FPG] ≥7 mmol/L), postadmission hyperglycemia (admission FPG <7 mmol/L but FPG ≥7 mmol/L after admission), and euglycemia (FPG <7 mmol/L throughout hospitalization) were compared for their clinical progress and outcomes. RESULTS: A total of 3225 patients were included in this study, 37.9% of whom developed acute hyperglycemia and 7.6% postadmission hyperglycemia. The presence of acute hyperglycemia, with or without known diabetes, was associated with increased risk of death (odds ratio [OR]: 1.63; 95% confidence interval [CI]: 1.29-2.05) compared with euglycemia. This effect, however, was only determined in female patients (OR: 2.15; 95% CI: 1.54-2.93). Insulin treatment of patients with SFTS and acute hyperglycemia without previous diabetes was associated with significantly increased mortality (OR: 1.58; 95% CI: 1.16-2.16). CONCLUSION: Acute hyperglycemia can act as a strong predictor of SFTS-related death in female patients. Insulin treatment of hyperglycemia in patients with SFTS without pre-existing diabetes has adverse effects.

[New aspects of myeloproliferative neoplasms: COVID-19 and myeloproliferative neoplasms].

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made the management of coronavirus disease-2019 (COVID-19) in patients with hematological disorders a new and important theme for hematologists. Patients with myeloproliferative neoplasms (MPNs) are susceptible to SARS-CoV-2 and are at an increased risk of death after the onset of COVID-19. Thus, infection prevention measures, including vaccination for all patients, are important. Patients with MPNs who have COVID-19 have a poor prognosis, as do patients with other hematological malignancies. The thrombogenic characteristics of MPNs increase the risk of venous thrombosis due to COVID-19. Anticoagulant therapy is adjusted according to the risk of each case after COVID-19 onset. However, thrombosis occurs at a high rate, especially in patients with essential thrombocythemia. Additionally, patients with myelofibrosis have an increased risk of death and bleeding. Ruxolitinib treatment poses a risk of SARAS-CoV-2 infection, and its abrupt discontinuation after infection is associated with an increased risk of death. The emerging evidence of COVID-19 has been quickly reflected in the available treatment recommendations and guidelines.

Prognostic Factors Associated With Mortality of Patients With COVID-19 Requiring Ventilator Management: A Retrospective Cohort Study.

Aim There are few reports on the prognostic factors associated with mortality in coronavirus disease (COVID-19) patients with critical disease. This study assessed prognostic factors associated with mortality of patients with critical COVID-19 who required ventilator management. Methods This single-center, retrospective cohort study used medical record data of COVID-19 patients admitted to an emergency ICU at a hospital in Japan between March 1, 2020 and September 30, 2021, and provided with ventilator management. Multivariable logistic regression was used to identify factors associated with mortality. Results Seventy patients were included, of whom 29 (41.4%) died. The patients who died were significantly older (median: 69 years) (interquartile range [IQR]: 47-82 years) than the patients who survived (62 years [38-84 years], p<0.007). In addition, patients who died were significantly less likely to have received steroid therapy than patients who survived (25 [86.2%] vs. 41 [100%], p=0.026). In the multivariable analysis, age was identified as a significant prognostic factor for mortality and the risk of death increased by 6% for every one-year increase in age (OR: 1.06; 95% CI: 1.00-1.13; p=0.048). Medical history was not a risk factor for death. Conclusion Age was a predictor of mortality in critically ill patients with COVID-19. Therefore, the indications for critical care in older patients with COVID-19 should be carefully considered.

A Lesson for the Future; Determining the Prognosis of the Pregnant Patients with COVID-19 in the Second Trimester? A Case Report.

Background: Coronavirus disease 2019 (COVID-19), the third coronavirus epidemic outbreak, has brought about a lot of concern about the pregnancy and the disease course, fatality rate, and the best management in severe cases. Early April 27, 2020, the first maternal mortality due to progressive COVID-19 infection was reported. Considering this challenging situation, the need for some comprehensive data on the main risk and predictive factors of disease progression is clear. Case Presentation: Here, we present our experience with 4 confirmed pregnant cases of COVID-19 in the second trimester, who showed typical COVID-19 symptoms like fever, cough, and myalgia. We aim to compare our findings with prior reports by reviewing the most recent and relevant studies.4 cases of COVID-19 induced respiratory discomfort in the second trimester of pregnancy were admitted to the intensive care unit. Most of the cases showed respiratory failure that led to intubation, but despite the similar initial presentation, they revealed widely. All of the required medical records are described here. Conclusion: Considering the limited information on this new COVID-19 clinical courses in pregnancy in comparison with two prior coronavirus outbreaks since the early 21 century, SARS-Cov and MERS-Cov, the possibility of poor pregnancy outcome has been confirmed, but there is debate on the effect of pregnancy and different management on disease progression. Taking into account the avail of this finding, our experiences, against prior belief, suggest pregnant patients are susceptible to severe morbidity and mortality, similar to report on pregnancies with SARS and MERS.

Characterization of coagulopathy and outcomes in cancer patients with severe COVID -19 illness: Longitudinal changes in hospitalized cancer patients.

There is a lack of data focused on the specific coagulopathic derangements in COVID-19 versus non-COVID-19 acutely ill cancer patients. Our objective was to characterize features of coagulopathy in cancer patients with active COVID-19 illness who required hospitalization at MD Anderson in the Texas Medical Center and to correlate those features with thrombotic complications, critical illness, and mortality within the first 30 days after hospital admission for COVID-19 illness. COVID-19 and non-COVID-19 hospitalized cancer patients, with at least five consecutive measures of PT, PTT, d-dimer, and CBC during the same period, were matched 1:1 to perform a retrospective analysis. We reviewed complete blood cell counts with differential, PT, PTT, fibrinogen, D-Dimer, serum ferritin, IL-6, CRP, and peripheral blood smears. Clinical outcomes were thrombosis, mechanical ventilation, critical illness, and death. Compared with matched hospitalized cancer patients without COVID-19, we found elevated neutrophil and lower lymphocyte counts in those with critical illness ( p =  0.00) or death ( p =  0.00); only neutrophils correlated with thrombosis. COVID-19 cancer patients with a platelet count decline during the hospital stay had more frequent critical illness ( p =  0.00) and fatal outcomes ( p =  0.00). Of the inflammatory markers, interleukin-6 showed consistently higher levels in the COVID-19 patients with poor outcomes. The findings of unique platelet changes and coagulopathy during severe COVID-19 illness in the cancer population are of interest to explore disease mechanisms and future risk stratification strategies to help with the management of cancer patients with COVID-19.

Serum Lactate Dehydrogenase Level as a Prognostic Factor for COVID-19: A Retrospective Study Based on a Large Sample Size.

Background: In this study, we investigated the relationship between serum lactate dehydrogenase (LDH) level and disease progression and prognosis of patients with COVID-19. Methods: We retrospectively reviewed the information of 1,751 patients with COVID-19 from Leishenshan Hospital in Wuhan, China. Univariate and multivariate Cox regression analyses as well as Logistics regression analyses, and Kaplan-Meier curves were used to determine the association between LDH levels and the prognosis of COVID-19 patients. Results: LDH was an independent risk factor for in-hospital death no matter it was taken as classified variable and continuous variable (all P = 0.001) but not for severe or critical illness status. The Kaplan-Meier curves for LDH level showed that an elevated level of LDH was associated with in-hospital death. Conclusions: In patients with COVID-19, the increased LDH level is associated with a higher risk of negative clinical prognosis and higher mortality. This will provide a reference for clinicians and researchers to understand, diagnose, and treat patients with COVID-19. Further prospective studies with larger sample sizes are needed to verify these findings.

Epidemiologic Characteristics of and Prognostic Factors for COVID-19 Among Hospitalized Patients: Updated Implications From Hubei Province, China.

Introduction: The roles of some indicators in the prognosis of patients with coronavirus disease-19 (COVID-19) remain unclear and controversial. This study aimed to explore the epidemiologic characteristics of and prognostic factors for COVID-19 to provide updated recommendations for its prevention, diagnosis, and treatment. Methods: For this retrospective study, demographic, epidemiologic, and clinical data were extracted from the medical records of patients admitted to the Maternal and Child Hospital of Hubei Province (Optical Valley) with COVID-19 between February 19, 2020, and March 19, 2020. The primary outcome was the prognosis that was determined at discharge as mentioned in the medical records. Descriptive statistics, univariate analyses, and stepwise logistic regression analysis were used for data analysis. Results: Of the 1,765 patients included, 93.1% were cured and the mortality was 1.8%. Univariate analyses identified 63 factors significantly associated with COVID-19 prognosis. Logistic regression analysis revealed that a poorer prognosis was associated with undergoing resuscitation, complex disease manifestations, consultation with outside specialists, elevated basophil or lymphocyte counts, an albumin (ALB)/globulin (A/G) ratio > 2.4, and elevated levels of serum aspartate aminotransferase (AST) or creatinine. Patients had a better prognosis if the following conditions were met: dry cough reported as an initial symptom, fatigue as a clinical manifestation, and a diagnosis based on laboratory testing. Conclusion: To prevent clinical deterioration, clinicians should provide special care to patients who underwent resuscitation, with a critical disease, or requiring consultation with outside specialists. Extra attention should be paid to patients with high basophil or lymphocyte counts, a high A/G ratio, and elevated AST or creatinine levels.

Differences in Dynamics of Lung Computed Tomography Patterns between Survivors and Deceased Adult Patients with COVID-19.

This study's aim was to investigate CT (computed tomography) pattern dynamics differences within surviving and deceased adult patients with COVID-19, revealing new prognostic factors and reproducing already known data with our patients' cohort: 635 hospitalized patients (55.3% of them were men, 44.7%-women), of which 87.3% had a positive result of RT-PCR (reverse transcription-polymerase chain reaction) at admission. The number of deaths was 53 people (69.8% of them were men and 30.2% were women). In total, more than 1500 CT examinations were performed on patients, using a GE Optima CT 660 computed tomography (General Electric Healthcare, Chicago, IL, USA). The study was performed at hospital admission, the frequency of repetitive scans further varied based on clinical need. The interpretation of the imaging data was carried out by 11 radiologists with filling in individual registration cards that take into account the scale of the lesion, the location, contours, and shape of the foci, the dominating types of changes, as well as the presence of additional findings and the dynamics of the process-a total of 45 parameters. Statistical analysis was performed using the software packages SPSS Statistics version 23.0 (IBM, Armonk, NY, USA) and R software version 3.3.2. For comparisons in pattern dynamics across hospitalization we used repeated measures general linear model with outcome and disease phase as factors. The crazy paving pattern, which is more common and has a greater contribution to the overall CT picture in different phases of the disease in deceased patients, has isolated prognostic significance and is probably a reflection of faster dynamics of the process with a long phase of progression of pulmonary parenchyma damage with an identical trend of changes in the scale of the lesion (as recovered) in this group of patients. Already known data on typical pulmonological CT manifestations of infection, frequency of occurrence, and the prognostic significance of the scale of the lesion were reproduced, new differences in the dynamics of the process between recovered and deceased adult patients were also found that may have prognostic significance and can be reflected in clinical practice.

The Ichikado CT score as a prognostic tool for coronavirus disease 2019 pneumonia: a retrospective cohort study.

BACKGROUND: The relationship between computed tomography (CT) and prognosis of patients with COVID-19 pneumonia remains unclear. We hypothesized that the Ichikado CT score, obtained in the first 24 h of hospital admission, is an independent predictor for all-cause mortality during hospitalization in patients with COVID-19 pneumonia. METHODS: Single-center retrospective cohort study of patients with confirmed COVID-19 pneumonia admitted at our institution between March 20th, 2020 and October 31st, 2020. Patients were enrolled if, within 24 h of admission, a chest CT scan, an arterial blood gas, a complete blood count, and a basic metabolic panel were performed. Two independent radiologists, who were blinded to clinical data, retrospectively evaluated the chest CT scans following a previously described qualitative and quantitative CT scoring system. The primary outcome was all-cause in-hospital mortality or survival to hospital discharge. Secondary outcomes were new requirements for invasive mechanical ventilation and hospital length of stay. Cox regression models were used to test the association between potential independent predictors and all-cause mortality. RESULTS: Two hundred thirty-five patients, 197 survivors and 38 nonsurvivors, were studied. The median Ichikado CT score for nonsurvivors was significantly higher than survivors (P < 0.001). An Ichikado CT score of more than 172 enabled prediction of mortality, with a sensitivity of 84.2% and a specificity of 79.7%. Multivariate analysis identified Ichikado CT score (HR, 7.772; 95% CI, 3.164-19.095; P < 0.001), together with age (HR, 1.030; 95% CI, 1.030-1.060; P = 0.043), as independent predictors of all-cause in-hospital mortality. CONCLUSIONS: Ichikado CT score is an independent predictor of both requiring invasive mechanical ventilation and all-cause mortality in patients hospitalized with COVID-19 pneumonia. Further prospective evaluation is necessary to confirm these findings. TRIAL REGISTRATION: The WCG institutional review board approved this retrospective study and patient consent was waived due to its non-interventional nature (Identifier: 20210799).

Lupus anticoagulant is an independent risk factor for non-thrombotic in-hospital mortality in COVID-19 patients.

BACKGROUND: Thromboembolic disease is a frequent cause of death during SARS CoV-2 infection. Lupus anticoagulant (LA) appears frequently during the acute phase of infection. It is not clear whether it is merely an epiphenomenon or whether it is related to the patients' outcome. METHODS: Prospective observational cohort of 211 patients (118 women, mean age 65 years, range: 18 to 99) hospitalized for COVID-19. All patients were tested for LA at admission and retested six months after discharge. RESULTS: The LA test was positive in 128 patients (60.7%). The survival probability at 31 days was clearly worse in the LA-positive group (60%) than in the LA-negative group (90%) (P = 0.023). This notable difference in survival was confirmed by multivariate analysis (HR 3.9, 95% CI 1.04-14.5, P = 0.04). However, it was not explained by differences in thrombotic events (three in either group, P = 0.6). LA-positive patients had higher ferritin, CRP and IL-6 levels, and lower PAFI ratio and lymphocyte and platelet counts. Six months after discharge, LA was negative in the vast majority of positive cases (94%). CONCLUSION: LA is an independent predictor of in-hospital mortality in COVID-19 patients. It is associated with inflammation and disease severity but not with thromboembolic events. This marker usually disappears at six months.

Red Blood Cell Distribution Width: Another Prognostic Factor for COVID-19?

The coronavirus disease 2019 (COVID-19) is a pandemic with a high rate of hospitalization, admission to intensive care units, and mortality. Identifying patients at the highest risk for severe disease is important to facilitate early, aggressive intervention. High red blood cell distribution width (RDW) values are associated with increased mortality in the general population in patients suffering from several conditions, including cardiovascular disease, sepsis, acute kidney injury, chronic obstructive pulmonary disease, and hepatitis B. Our study aimed to determine whether RDW levels in all COVID-19 confirmed cases admitted to the Patras University Hospital, Greece, was an independent prognostic factor of hospitalization and disease outcome.

Spontaneous Pneumomediastinum in Patients Diagnosed with COVID-19: A Case Series with Review of Literature.

BACKGROUND: Spontaneous pneumomediastinum (SPM) is a rare condition defined by the presence of air in the mediastinum in the absence of traumatic or iatrogenic injury. Although the imaging findings and complications of SARS-CoV-2 infection have been reported many times, there are few reports of the prevalence and outcomes of patients with SPM. PURPOSE: In this paper, we aimed to illustrate the different manifestations, management, and outcome of three cases of SPM in COVID-19 patients and provide an extensive review available literature. MATERIALS AND METHODS: Detailed report of patients' demographics, clinical presentation, management, and outcome of three cases of COVID-19 induced SPM seen in our institution was provided. Additionally, literature search was employed through March 2021 using Pubmed and Google scholar databases where a total of 22 articles consisting of 35 patients were included. RESULTS: Statistical analysis of the reviewed articles showed that SPM in COVID-19 occurs in patients with a mean age of 55.6 ± 16.7 years. Furthermore, 80% of the 35 patients are males and almost 60% have comorbidities. Intriguingly, SPM in COVID-19 is associated with a 28.5% mortality rate. These findings are consistent with our case series and are different from previous reports of SPM in non-COVID-19 cases where it most commonly occurs in younger individuals and has a self-limiting course with a good outcome. CONCLUSION: Therefore, SPM in COVID-19 patients occurs in older patients and is potentially associated with a higher mortality rate. Further studies are necessary to assess its role as a prognostic marker of poor outcome.

Systemic lupus erythematosus presenting as non-resolving pneumonia: a case report.

BackgroundSystemic lupus erythematosus (SLE) is a rheumatological disorder with a heterogeneous clinical presentation and disease course. Case presentationWe report a case concerning a young woman with pleuropneumonia, non-responsive to conventional antibiotic therapy, who was, upon further inquiry and passage of time, diagnosed with SLE. Key pointsBy means of this case, we would like to emphasize the clinical implications and prognostic significance of lymphopenia in patients with SLE. Moreover, we attempt to make the reader aware of some of the protean manifestations of SLE and we would like to raise suspicion of acute lupus pneumonitis by demonstrating a case of a young female with non-resolving pneumonia.

Treatment outcomes and prognostic factors for non- malignancy associated secondary hemophagocytic lymphohistiocytosis in children.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome that requires prompt diagnosis and appropriate treatment. A risk-stratification model that could be used to identify high-risk pediatric patients with HLH who should be considered for second-line therapies, including salvage regimens and allogeneic hematopoietic cell transplantation (HCT), was developed. METHODS: The medical records of 88 pediatric patients (median age 1.4 years, range 0.2-15 years) with non-malignancy associated secondary HLH were retrospectively reviewed. Treatment strategies included dexamethasone, etoposide, and cyclosporine. RESULTS: Survival analysis showed HLH patients with infections other than Epstein-Barr virus (EBV) and unknown causes experienced better 5-year overall survival (OS) than patients with HLH due to autoimmune disease, EBV or immunodeficiency (76% vs. 65, 33.3, 11%, p < 0.001). On multivariate analysis, among all patients, non-response at 8 weeks was the most powerful predictor of poor OS. When treatment response was excluded, hemoglobin < 60 g/L and albumin < 25 g/L at diagnosis were associated with poor OS. In patients with EBV-HLH, hemoglobin < 60 g/L at diagnosis was associated with poor OS. A prognostic risk score was established and weighted based on hazard ratios calculated for three parameters measured at diagnosis: hemoglobin < 60 g/L (2 points), platelets < 30 × 109/L (1 point), albumin < 25 g/L (2 points). Five-year OS of low-risk (score 0-1), intermediate-risk (score 2), and poor-risk (score ≥ 3) patients were 88, 38, and 22%, respectively (p < 0.001). CONCLUSIONS: These findings indicate that clinicians should be aware of predictive factors at diagnosis and consider 8-week treatment response to identify patients with high-risk of disease progression and the need for second-line therapy and allogeneic HCT.

Elevated fibrinogen and fibrin degradation product are associated with poor outcome in COVID-19 patients: A meta-analysis.

INTRODUCTION: COVID-19 is a systemic infection with a significant impact on coagulation which manifests in thromboembolism. There is an unknown relationship of which coagulation profile parameter at presentation has an association with poor outcome in COVID-19. OBJECTIVE: This meta-analysis aimed to determine the relationship between fibrinogen and FDP with poor outcome in COVID-19 patients. METHODS: A systematic search of all observational studies or trials involving adult patients with COVID-19 that had any data fibrinogen or FDP on admission was carried out using the PubMed, Science Direct, Scopus, ProQuest, and MedRxiv databases. We assessed the methodological quality assessment using the NIH Quality Assessment Tool. We performed random-effects inverse-variance weighting analysis using mean difference (MD). RESULTS: A total of 17 studies (1,654 patients) were included in this meta-analysis. It revealed a higher mean of fibrinogen levels on admission in patients with severe case compared to those with non-severe case (MD = 0.69, [95% CI: 0.44 to 0.94], p < 0.05; I2 = 72%, p < 0.05). Non-survivor group had a pooled higher mean difference of fibrinogen values on admission (MD = 0.48 [95% CI: 0.13 to 0.83], p < 0.05; I2 = 38%, p = 0.18). Higher FDP on admission was found in poor outcome (composite of severity, critically ill, and mortality) compared to good outcome (4 studies, MD = 4.84 [95% CI: 0.75 to 8.93], p < 0.05; I2 = 86%, p < 0.05). CONCLUSION: Elevated fibrinogen and FDP level on admission were associated with an increase risk of poor outcome in COVID-19 patients.